Immune System Suppression with Steroids for Hemangiomas

Action Points

Explain to interested parents that immune suppression occurs when children with hemangiomas receive corticosteroid treatment, but this is largely reversible.

But explain that vaccine titers will need to be checked and additional vaccinations provided if the titers are low.

Corticosteroid treatment of infantile hemangiomas led to profound but largely reversible immune suppression in young infants, results of a small prospective study showed.

Absolute numbers of B lymphocytes and CD4+ T cells fell significantly by week eight of corticosteroid administration and CD8+ T cells dropped by week 16, Michael E. Kelly, MD, PhD, and colleagues from the Medical College of Wisconsin in Milwaukee reported online in the Archives of Dermatology.

Most infantile hemangiomas -- benign tumors consisting of proliferating endothelial cells that appear during the first months of life -- are self-limited, but 10% to 38% require treatment because of potential complications.

Corticosteroids are a standard treatment when there are life-threatening or functional complications, but multiple adverse effects associated with adrenal suppression and immune system compromise are presumed to occur.

No drug has been approved by the FDA for the treatment of these hemangiomas, and there are no management guidelines or objective outcome measures.

To address these uncertainties, Kelly and colleagues enrolled 16 patients whose mean age was 2.9 months. Most were girls and all were white; the head and neck were the most common sites of the lesions.

The average size of the hemangiomas was 24.3 cm2, and the most common reasons for treatment were threat to vision, ulceration, and potential for disfigurement.

The numbers of lymphocytes were normal at baseline for all patients.

Treatment involved oral administration of prednisolone sodium phosphate suspension (15 mg/5 mL) each morning, starting with a dose of 2.5 mg/kg and adjusted according to response.

During a mean treatment duration of 22 weeks, 50% of the infants had a partial response, which was defined as a decrease in size of the hemangioma of more than 30%, and the other 50% remained stabilized.

In assessing immunologic status, the investigators found that "corticosteroid administration resulted in a rapid and sustained reduction in the numbers of all B- and T-cell lymphocyte subpopulations when compared with values at baseline and values for age-matched controls."

For instance, CD4+ counts fell from a mean of 3,076/μL at baseline to 751/μL at week eight.

In contrast, the number of CD56+ natural killer cells did not appear to be affected.

Within three months of stopping the corticosteroid treatment, levels of all lymphocyte subpopulations had normalized.

The investigators also looked at the impact of treatment on immune function by measuring antibody generation to antigens found in childhood vaccines.

Three months after completion of therapy, only five of 16 previously immunized patients had protective tetanus titers, while 13 had protective diphtheria titers.

The authors noted that it was unclear why there would be a discrepancy in the number of patients who had protective titers for the two different antigens, but suggested that there may be differences in mechanisms of antibody production or corticosteroid sensitivity in the response process.

They recommended that all patients who receive corticosteroids during the infancy immunization period have titers checked and additional vaccines be considered if titers are inadequate.

Complications of corticosteroid treatment other than immune suppression included:

Hyperphagia and weight gain in 12 patients

Disturbances in linear growth in 10

Irritability and sleep disturbances in 10

Hypertension in two

Most of these adverse events were seen with higher doses, decreasing in frequency and severity when the drug was tapered.

Nonetheless, the authors cautioned, the effects of corticosteroids are wide ranging and physicians caring for these patients need to monitor for potentially serious risks.

There also are concerns with infection. No serious or repeated infections were seen in this study, but low CD4+ lymphocyte counts are associated with many potentially serious infections, including Pneumocystis jiroveci (formerlycarinii)pneumonia.

There have been at least three case reports of life-threatening P. jirovecipneumonia and one death in children with hemangiomas treated with corticosteroids, so the authors suggested that consideration be given to prophylaxis with trimethoprim-sulfamethasoxazole.

They concluded that antigen-specific immunoglobulin generation is significantly impaired following corticosteroid treatment. While lymphocyte counts promptly recovered following cessation of treatment, impairment of antibody generation persisted, through an unknown mechanism.

"Future studies will include the enumeration of CD27 and CD70 cells as markers of B- and T-memory lymphocytes, respectively, to begin to elucidate this mechanism," they said.

The study was supported by a William Weston Research Award from the Society of Pediatric Dermatology.

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